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E-钙粘素基因启动子甲基化及该基因表达与前列腺癌病理分级的关系

A specific methylation pattern of the E-cadherin gene promoter is associated with its expression and the pathological grades in prostate cancer

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【作者】 李龙承张旭陈忠欧阳金芝杜广辉杨为民叶章群

【Author】 LI Longchen, ZHANG Xu, CHEN Zhong, et al. Department of Urology, Tongji Hospital, Tongji Medical University, Wuhan 430030, China

【机构】 同济医科大学附属同济医院泌尿外科同济医科大学附属同济医院内分泌科

【摘要】 目的 探讨E 钙粘素 (E cad)基因及其启动子上CpG位点甲基化与前列腺癌细胞E cad基因失活的关系。方法 通过显微解剖技术收集 35例前列腺癌组织细胞标本 ,并按病理分级分为低级别组 (Ⅰ~Ⅱ ) 15例和高级别组 (Ⅲ~Ⅴ ) 2 0例 ,采用硫酸氢钠基因组测序法检测E cad基因甲基化状态 ,采用免疫组织化学方法检测癌细胞内E cad蛋白表达 ,分析E cad基因甲基化与其表达、肿瘤病理分级间的关系。结果 低级别的前列腺癌和高级别肿瘤E cad基因甲基化阳性率分别为 33 % (5 /15 )和 70 % (14/ 2 0 ) ,低级别标本甲基化主要位于外显子区域 ;而在高级别标本中 ,启动子区域也发生甲基化。免疫组织化学染色 ,在甲基化阳性的细胞 ,阴性染色的癌细胞比例随病理级别的增高而增加。结论 前列腺癌E cad基因高甲基化状态 ,特别是启动子区域甲基化是引起该基因失活并导致前列腺癌浸润进展的因素之一。

【Abstract】 Objective\ To study the relationship between CpG methylation of E-cadherin (E-cad) promoter region and inactivation of the E-cad gene expression in prostate cancer. Methods\ Thirty-five patients with prostate cancer were divided into low-grade (Ⅰ~Ⅱ) group ( n =15) and high-grade (Ⅲ~Ⅴ) group ( n =20) according to pathological grades. The methylation status of E-cad gene in microdissected tissues was tested by using the bisulfite genome sequencing technique and the expression of E-cad in prostate cancer cells detected by using immunostaining method. The relationship between the methylation of E-cad and E-cad expression or the pathological grades of the tumors was analyzed. Results\ The overall methylation of E-cad was evident in 33% of low-grade samples (5/15) and 70% of high-grade prostate cancer samples (14/20), and it was correlated with either absent or reduced E-cad immunostaining. Methylation in low-grade tumors was found mainly in the exon region, whereas in high-grade tumors, methylation was also found in the promoter region. Conclusion\ Hypermethylation of E-cad in prostate cancer, especially in the promoter region, is a common event that leads to the inactivation of the E-cad gene and in turn contributes to the progression of prostate cancer.\;

【关键词】 E钙粘素甲基化前列腺癌
【Key words】 E-cadherin\ Methylation\ Prostate cancer
  • 【文献出处】 中华实验外科杂志 ,CHINESE JOURNAL OF EXPERIMENTAL SURGERY , 编辑部邮箱 ,2000年05期
  • 【分类号】R737.25
  • 【被引频次】17
  • 【下载频次】147
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